High serum folate levels associated with greatly reduced acute coronary event incidence
A study published in the August 2004 issue of The American Journal of Clinical Nutrition examined folate and homocysteine levels in a group of Finnish men and found that folate, but not homocysteine, had a significant inverse association with the risk of experiencing an acute coronary event (defined as a heart attack or prolonged episode of chest pain). The study analzyed subjects in the Kuopio Ischaemic Heart Disease Risk Factor Study, which enrolled 2,682 men aged 42 to 60 between 1984 and 1989. The current study followed 1027 participants for an average of 7.7 years, beginning in 1991-1993. Blood samples drawn at the beginning of the study provided serum folate and total homocysteine levels.
During the follow-up period 114 acute coronary events were documented in 61 subjects. Men who experienced acute coronary events were older, had higher systolic blood pressures and higher cholesterol levels, and had lower lycopene levels than those who remained event-free. Those whose serum levels were in the highest one-third of the group had a risk of undergoing an acute coronary event that was 65 percent lower than that experienced by men whose folate was in the lowest third. In contrast with other studies, homocysteine levels were not associated with acute coronary event risk in this study, although when smokers were separately analzyed, high homocysteine was associated with almost double the risk of an acute coronary event compared to the risk experienced by smokers with low homocysteine.
The authors recommend intervention studies to determine the effect of folic acid supplements on cardiovascular health, and to ascertain whether the vitamin’s ability to reduce homocysteine prevents heart disease or if high homocysteine and low folate levels are markers of atherosclerosis or an unhealthy lifestyle.
Smoking-induced vitamin A deficiency may be the cause of emphysema
While studying the relationship between inflammation of the lung and vitamin A, Kansas State University researchers accidentally uncovered a link between vitamin A deficiency and emphysema in smokers. In early research published in the Journal of Nutrition in the year 2000, Kansas State associate professor of human nutrition Richard C Baybutt and colleagues found that rats who received a diet deficient in vitamin A developed emphysema, a disease that is found primarily in people who smoke. A study published in the August 2003 issue of the same journal revealed that rats exposed to cigarette smoke developed vitamin A deficiency as well as severe emphysema. When the smoke-exposed rats were given high vitamin A diets, the areas of emphysema were reduced.
A carcinogen found in cigarettes known as benzopyrene which has been found to deplete vitamin A in the lungs and livers of rats is the likely cause of smoking induced vitamin A deficiency in humans. Vitamin A and other retinoids regulate lung development and the maintenance of the epithelium in the alveoli (the small air sacks within the lungs). The vitamin A metabolite all-trans-retinoic acid has demonstrated an ability to reverse emphysema in laboratory animals in whom the disease was induced.
Dr Baybutt explained the findings: "When the lung content of vitamin A was low, the score of emphysema was high. So, the hypothesis is that smokers develop emphysema because of a vitamin A deficiency . . . There are a lot of people who live to be 90 years old and are smokers. Why? Probably because of their diet. The implications are that those who start smoking at an early age are more likely to become vitamin A deficient and develop complications associated with cancer and emphysema. And if they have a poor diet, forget it."
Cancer expert calls on FDA to help reduce colon cancer and osteoporosis
In an article published in the August 1 2004 issue of the American Journal of Clinical Nutrition, cancer prevention expert Harold Newmark of Rutgers University and colleagues have submitted a call to action to the U.S. Food and Drug Administration (FDA) to help prevent deaths from colon cancer and fractures resulting from osteoporosis. Their proposal involves mandatory enrichment of cereal products such as flour with calcium and vitamin D in addition to the other nutrients currently mandated under U.S. law. Their idea is based on the well-known ability of calcium and vitamin D to contribute to the prevention of osteoporosis, and more recent findings concerning the protective effect of the nutrients against colon cancer. Studies have shown that calcium helps inactivate the fatty acids in the colon that are present in individuals who consume high fat diets, and which can produce cell damage that can initiate cancer. Vitamin D aids this process by increasing calcium absorption.
Newmark and colleagues estimate that implementation of this measure would save 11,000 American lives and three billion dollars in health care costs per year. Currently, many Americans are deficient in both calcium and vitamin D, and the incidence of colon cancer and osteoporosis is high.
Dr Newmark, who is an adjunct professor-in-residence at the Susan Lehman Cullman Laboratory for Cancer Research of Rutgers, The State University of New Jersey, stated, “"For about 10 cents per person per year, we can use existing technology to correct all this. We believe that the time has come for a full scientific review of cereal-grain enrichment with calcium and vitamin D as a low-cost, safe and useful route for the reduction of osteoporosis and colon cancer in the United States in both men and women."
CDC finds folic acid mandate successful in helping to prevent birth defects, but more effort needed
The July 21 2004 issue of the Journal of the American Medical Association (http://jama.ama-assn.org/) published a report from the U.S. Centers for Disease Control (CDC) which documented the decrease in neural tube defects and anencephaly (birth defects of the spine and brain) following the folic acid mandate issued by the U.S. Public Health Service in 1992. This mandate recommended that women of reproductive age improve their dietary habits, that foods be fortified with folic acid, and that dietary supplements containing folic acid be utilized. In January of 1998, mandatory folic acid fortification of cereal grain products went into effect in the United States.
The CDC estimated that spina bifida affected 2,490 pregnancies and anencephaly affected 1,640 pregnancies annually from 1995 to 1996 (before folic acid food fortification was initiated), creating a total of 4,130 neural tube defects. Following fortification, these numbers dropped to an estimated 1,640 cases of spina bifida and 1,380 anencephaly-affected pregnancies, bringing the total of neural tube defects to 3,020, which is a 27 percent decline. These results are encouraging, but need to be improved to meet the national health objective of reducing neural tube defects by 50 percent by the year 2010.
In an editorial note the CDC recommends greater effort to increase consumption of 400 micrograms folic acid per day by women of reproductive age. They observe that health care providers can have a significant impact on increasing the use of folic acid supplements and note that 88 percent of reproductive-aged women reported that they would take a supplement that contains folic acid if their health-care providers recommended it, but only 37 percent reported that they received such a recommendation.
High dose vitamin D safe and effective in improving winter wellbeing
A study appearing in the online publication Nutrition Journal on July 19 2004 has found that supplementation with high doses of vitamin D are safe and effective in improving wellbeing in individuals deficient in the vitamin.
In this report, researchers from the University of Toronto and Mount Sinai Hospital, also in Toronto, summarized the results of two studies involving individuals with low summer serum levels of 25-hydroxy-vitamin D. (Serum levels of vitamin D are typically higher during the summer months than in winter.) The first study administered 600 international units (IU) per day, which is considered to be the adequate intake for vitamin D, or a high dose of 4000 IU per day, to 46 participants from December 2001 through November 2002. The second study administered 600 IU or 4000 IU vitamin D to 66 participants from December 2002 to February 2003. A series of questions on depressive symptoms were answered by the subjects at the beginning of both studies and at three months, which provided information on the participants’ sense of wellbeing. Blood samples were analyzed for serum vitamin D, parathyroid hormone and calcium levels.
In both studies, vitamin D supplementation significantly elevated serum vitamin D, predictably to a greater degree in the group that received the higher dose of the vitamin. Supplementation with the vitamin also lowered plasma parathyroid hormone and did not affect calcium levels any of the participants. In the first study, participants who received the higher dose of vitamin D experienced a significantly greater improvement in wellbeing compared to those who received the lower dose. Winter wellbeing improved in both groups who participated in the second study.
This study confirms the efficacy of vitamin D on depressive symptoms, and confirms the vitamin’s safety at a relatively high dose.
Soy isoflavones reduce cognitive decline in older rats
The July 2004 Journal of Nutrition (http://www.nutrition.org/) published the findings of researchers in Korea on the benefit of soy isoflavones in reducing cognitive decline in older male rats. Phytoestrogens such as soy isoflavones have been found in some human studies to improve cognitive function. Estrogen receptors found in the brain may have an affinity for these plant compounds.
Forty-eight ten month old male rats were given diets that contained a low amount of isoflavones, a high amount of isoflavones, or a control diet for sixteen weeks. At the study’s conclusion, activity of the cholinergic enzyme choline acetyltransferase was higher in two areas of the brain the groups receiving the lower amount of isoflavones and in one area in the group that received the higher amount, compared to the control group. Choline acetyltransferase is an enzyme that controls the production of acetylcholine, a neurotransmitter that is decreased in the aging brain and Alzheimer’s disease. Another enzyme, acetylcholine esterase, which breaks down acetylcholine, was found to have lower activity in several areas of the brain in the groups receiving soy isoflavones compared to those that did not receive the compounds.
When memory and learning performance was evaluated using a water maze test, rats who received the lower dose of isoflavones demonstrated superior performance compared to the control group. The authors suggest that the benefits provided by low but not high isoflavone diets may be due to a response specific to male versus female rats, based on the observation that in previous research, a high phytoestrogen diet improved memory in female rats but impaired it in males. They conclude that “soy isoflavones can ameliorate deficits in memory tasks resulting from the loss of cholinergic input to the hippocampus or cholinergic degeneration in elderly male rats.”
Soy isoflavones’ benefit on bone mineral content is greater for some women than others
In a study published in the journal Menopause (2004, volume 11 no 3), researchers from the Chinese University of Hong Kong found that the benefit of isoflavones derived from soy on the rate of change of bone mineral content in postmenopausal women was more pronounced among women whose menopause had occurred four or more years previously, who had a low body weight or who had a lower calcium intake (factors known to be involved in bone loss). Laboratory studies have shown improvement in bone mass when animals were given soy protein or isoflavones, and studies in postmenopausal women have established positive associations between soy protein or isoflavone consumption and improvements in bone mass.
In a double-blind study, 203 postmenopausal women aged 48 to 62 were randomized to received 500 milligrams calcium plus 125 international units vitamin D per day combined with a placebo, 40 milligrams soy isoflavones, or 80 milligrams soy isoflavones for one year. Interviews with the participants provided data on years since menopause, and food frequency questionnaires were used to calculate calcium intake. Whole body, spine, and hip bone mineral content and bone mineral density were measured at the beginning and end of the study.
The team found that 80 milligrams per day isoflavones had a significant favorable effect on bone mineral content rate of change in the total hip and trochanter (part of the bone in the upper leg). This effect was more marked in participants who were later in menopause, who weighed less, or who had a lower calcium intake
Omega-3 fatty acid intake associated with lower levels of inflammatory and endothelial activation biomarkers
The July 2004 Journal of Nutrition (http://www.nutrition.org/) published the findings of Harvard researchers that increased consumption of omega-3 fatty acids in the diet is associated with lower levels of inflammation and endothelial activation. Dysfunction of the endothelium, which is the inner lining of the blood vessel wall, is an early event in the development of atherosclerosis. Omega-3 fatty acids have been found to provide a protective benefit against cardiovascular disease, and in addition to reducing triglycerides, platelet aggregation and cardiac arrhythmias, appear to play yet other roles in heart disease prevention.
Food frequency questionnaires completed in1986 and 1990 by 727 participants in the Nurses’ Health study were evaluated for levels of the omega-3 fatty acids alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Blood samples collected between 1989 and 1990 provided measurements of the inflammatory and endothelial activation markers C-reactive protein, interleukin-6, E-selectin, soluble tumor necrosis factor receptor 2 (sTNFR-2) and soluble cell adhesion molecules (sICAM-1 and sVCAM-1).
Alpha-linolenic acid consumption was found to be inversely associated with plasma C-reactive protein, interleukin-6 and E-selectin levels, while EPA and DHA intake was inversely related to soluble cell adhesion molecule levels. Total fatty acids were inversely related to all of these levels.
The authors suggest that a possible pathway used by omega-3 fatty acids to inhibit inflammation and endothelial activation is by decreasing the body’s production of hydrogen peroxide, which is involved in the inflammatory process. They believe that their findings may provide a partial explanation for the benefit of omega-3 fatty acids in cardiovascular disease prevention.
Study fails to find increased risk of breast or uterine cancer in monkeys fed soy isoflavones
One of the concerns often voiced in regard to soy isoflavone consumption is that these plant estrogens could stimulate breast or uterine cancer in women. A study published in the current issue of The Journal of Clinical Endocrinology & Metabolism may help alleviate some of these concerns.
For a three year period, researchers from Wake Forest University Baptist Medical Center fed postmenopausal monkeys a soy enriched diet that containing the human equivalent of 129 milligrams isoflavones per day, a diet high in soy without isoflavones, or soy minus isoflavones combined with the estrogen replacement drug known as Premarin. Cancer risk markers such as breast density, numbers of dividing breast and uterine cells, and endogenous estrogen levels were monitored.
They found that the monkeys who consumed soy and Premarin experienced increased levels of all risk markers, while those who received isoflavones not only did not experience an increase in the markers, but actually produced lower levels of their own estrogen.
Lead researcher Charles E. Wood, DVM, commented, "Evidence from observational studies in women indicates that soy intake may help prevent breast cancer. But there has still been reluctance to conduct research studies in women because of concerns that isoflavones may stimulate breast cell growth and increase the risk of breast cancer. This is convincing evidence that at dietary levels, the estrogens found in soy do not stimulate cell growth and other markers for cancer risk. The findings should be especially interesting to women at high risk for breast cancer who take soy products."
Dr Wood cautioned that the findings apply to healthy breast tissue and not to women with breast cancer. "A big unanswered question is whether it is safe for breast cancer survivors to turn to soy," he added.
Healthy selenium levels associated with lower homocysteine in older individuals
The July 1 2004 issue of the American Journal of Clinical Nutrition published the discovery by researchers in Spain of an inverse association between plasma total homocysteine concentrations and selenium levels in an older population. Deficient levels of selenium have been implicated in the development of cardiovascular disease, although its mechanism of action has not been fully explored.
Eighty-five men and 117 women with an average age of 73.6 and 76.4, respectively, participated in the current study. Dietary protein and energy intake was ascertained by the completion of food frequency questionnaires by the participants. Fasting blood samples were analyzed for plasma homocysteine, serum folate, vitamin B12, creatinine, and selenium.
Serum folate and serum selenium levels were found to be inversely related to homocysteine concentrations, with serum selenium having a greater effect than folate. Protein intake was also found to have an inverse association with homocysteine in men.
While serum folate's inverse relationship to homocysteine levels is well established, a similar relationship for selenium has been suggested by a small number of animal studies. The researchers note that the focus of investigation into selenium's benefit in heart disease has been the mineral's antioxidant properties, and that the current study suggests another mechanism for selenium in cardiovascular disease prevention. Further experimental and observational studies are needed to confirm the benefit of selenium in lowering homocysteine.